肿瘤抑制物黄烷酮通过 PARP、PI3K/AKT/mTOR 和 MAPK/ERK 信号通路抑制人卵巢癌细胞增殖并诱导其凋亡。
Anti-Tumor Xanthones from Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells.
机构信息
Department of Emergency and Critical Care Medicine, Jin Shan Hospital, Fudan University, Shanghai 201508, People's Republic of China.
Department of Neonatology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
出版信息
Drug Des Devel Ther. 2020 Sep 25;14:3965-3976. doi: 10.2147/DDDT.S258811. eCollection 2020.
BACKGROUND
Ovarian cancer (OC) is a serious public health concern in the world. It is important to develop novel drugs to inhibit OC.
PURPOSE
This study investigated the isolation, elucidation, efficiency, molecular docking, and pharmaceutical mechanisms of xanthones isolated from .
METHODS
Xanthones were isolated, and purified by different chromatography, including silica gel, reversed-phase silica gel (ODS-C), and semipreparative HPLC, then identified by analysis of their spectral data. Three xanthones were estimated for their efficiency on the human OC cells HEY and ES-2. was found to be the most potent cytotoxic xanthones of those tested. Further, its mechanisms of action were explored by molecular docking, cell apoptosis, and Western blotting analysis.
RESULTS
Bioassay-guided fractionation of the fruits of led to the separation of a new xanthone named nujiangexanthone G () and two known xanthones. Among these, isojacareubin () exhibited the most potent cytotoxic compound against the HEY and ES-2 cell lines. The analysis of Western blot suggested that inhibited OC via regulating the PARP, PI3K/AKT/mTOR, and ERK/MAPK signal pathways in the HEY cell lines.
CONCLUSION
In conclusion, isojacareubin () might be a potential drug for the treatment of OC.
背景
卵巢癌（OC）是全球严重的公共卫生问题。开发新型药物抑制 OC 非常重要。
目的
本研究从 中分离、阐明、评估、分子对接并探讨了分离得到的酮类化合物的药效学机制。
方法
采用硅胶、反相硅胶（ODS-C）和半制备 HPLC 等不同色谱法对酮类化合物进行分离和纯化，通过分析其光谱数据进行鉴定。评估三种酮类化合物对人 OC 细胞 HEY 和 ES-2 的效力。结果表明，在所测试的酮类化合物中， 是最有效的细胞毒性酮类化合物。进一步通过分子对接、细胞凋亡和 Western blot 分析探索其作用机制。
结果
基于生物活性导向的分离，从 的果实中分离得到一种新的酮类化合物，命名为怒江酮 G（ ）和两种已知的酮类化合物。其中，异乔松脂素（ ）对 HEY 和 ES-2 细胞系表现出最强的细胞毒性。Western blot 分析表明， 通过调节 PARP、PI3K/AKT/mTOR 和 ERK/MAPK 信号通路抑制 OC。
结论
总之，异乔松脂素（ ）可能是治疗 OC 的潜在药物。
Zotero 插件